title: Rosmarinic acid inhibits chemical hypoxia-induced cytotoxicity in primary cultured rat hepatocytes.
abstract: We examine the effect of rosmarinic acid (RA) in chemical hypoxia-induced injury in rat hepatocytes. Cell viability was significantly decreased by cobalt chloride (CoCl2), a well-known hypoxia mimetic agent in a time- and dose- dependent manner. RA pretreatment before exposure to CoCl2 significantly attenuated the CoCl2-induced decrease of cell viability. Additionally, pretreatment with RA potentiated the decrease of Bcl-2 expression and attenuated the increase of Caspase-3 expression by CoCl2. CoCl2 treatment resulted in an increase of intracellular ROS generation, which is inhibited by RA or N-acetyl-cysteine (NAC, a ROS scavenger), and p38MAPK phosphorylation, which is also blocked by RA or NAC. CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3 expression was attenuated by RA, NAC and SB203580 (p38MAPK inhibitor). CoCl2-induced decrease of cell viability was also attenuated by RA, NAC and SB203580 pretreatment. Additionally, RA inhibited CoCl2-induced COX-2 expression and prostaglandin E2 (PGE2) secretion. Similar to the effect of RA, both NAC and NS-398 (COX-2 inhibitor) blocked CoCl2-induced COX-2 expression and PGE2 secretion. NS-398 attenuated not only CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3 expression, but decrease of cell viability. Taken together, RA protects primary cultured rat hepatocytes against CoCl2-induced cell injury through inhibition of ROS-activated p38MAPK and COX-2/PGE2 pathway.
authors.affiliation: Department of Molecular Physiology, College of Pharmacy, Kyungpook National University, Taegu, 702-701, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Song
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D053630:Depsides / Q000302:isolation & purification / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D000097123:Rosmarinic Acid